Leuprorelin Acetate Every-3-Months Depot Versus Cyclophosphamide, Methotrexate, and Fluorouracil As Adjuvant Treatment in Premenopausal Patients With Node-Positive Breast Cancer: The TABLE Study

Purpose Ovarian suppression with luteinizing hormone–releasing hormone (LHRH) agonists is an effective adjuvant treatment for premenopausal women with estrogen receptor (ER) –positive breast cancer. Whereas monthly LHRH agonist therapy has been well established, the value of every-3-months (3-monthly) formulations is unclear. Patients and Methods This randomized phase III trial was performed to compare the 3-monthly depot LHRH agonist leuprorelin acetate (LAD-3M; n = 299) and chemotherapy with cyclophosphamide, methotrexate, and fluorouracil (CMF; n = 300) in pre- or perimenopausal patients with ER-positive, node-positive breast cancer. Results With a median follow-up of 5.8 years, recurrence-free survival was similar for patients treated with LAD-3M or CMF (hazard ratio [HR], 1.19; 95% CI, 0.94 to 1.51; P = .15). There was no substantial heterogeneity in the relative treatment effect among subgroups defined by age, progesterone receptor (PR) status, nodal status, hormone levels, or menstrual recovery after treatment. Exploratory overall survival analysis favored LAD-3M (HR, 1.50; 95% CI, 1.13 to 1.99; P = .005). Chemotherapy-related adverse effects such as nausea, vomiting, and alopecia were more common with CMF, whereas symptoms of estrogen suppression such as hot flushes and sweating were initially more pronounced with LAD-3M. Conclusion The 3-monthly depot LHRH-agonist leuprorelin acetate is an effective adjuvant treatment in premenopausal patients with hormone receptor–positive, node-positive breast cancer that is not inferior to CMF.

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Goserelin Versus Cyclophosphamide, Methotrexate, and Fluorouracil as Adjuvant Therapy in Premenopausal Patients With Node-Positive Breast Cancer: The Zoladex Early Breast Cancer Research Association Study

Journal of Clinical Oncology ◽

10.1200/jco.2002.05.042 ◽

2002 ◽

Vol 20 (24) ◽

pp. 4628-4635 ◽

Cited By ~ 242

Author(s):

W. Jonat ◽

M. Kaufmann ◽

W. Sauerbrei ◽

R. Blamey ◽

J. Cuzick ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Research ◽

Side Effects ◽

Association Study ◽

Early Breast Cancer ◽

Research Association ◽

Node Positive ◽

Er Positive ◽

Premenopausal Patients ◽

Positive Breast Cancer

PURPOSE: Current adjuvant therapies have improved survival for premenopausal patients with breast cancer but may have short-term toxic effects and long-term effects associated with premature menopause. PATIENTS AND METHODS: The Zoladex Early Breast Cancer Research Association study assessed the efficacy and tolerability of goserelin (3.6 mg every 28 days for 2 years; n = 817) versus cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy (six 28-day cycles; n = 823) for adjuvant treatment in premenopausal patients with node-positive breast cancer. RESULTS: Analysis was performed when 684 events had been achieved, and the median follow-up was 6 years. A significant interaction between treatment and estrogen receptor (ER) status was found (P = .0016). In ER-positive patients (approximately 74%), goserelin was equivalent to CMF for disease-free survival (DFS) (hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.84 to 1.20). In ER-negative patients, goserelin was inferior to CMF for DFS (HR, 1.76; 95% CI, 1.27 to 2.44). Amenorrhea occurred in more than 95% of goserelin patients by 6 months versus 58.6% of CMF patients. Menses returned in most goserelin patients after therapy stopped, whereas amenorrhea was generally permanent in CMF patients (22.6% v 76.9% amenorrheic at 3 years). Chemotherapy-related side effects such as nausea/vomiting, alopecia, and infection were higher with CMF than with goserelin during CMF treatment. Side effects related to estrogen suppression were initially higher with goserelin, but when goserelin treatment stopped, reduced to a level below that observed in the CMF group. CONCLUSION: Goserelin offers an effective, well-tolerated alternative to CMF in premenopausal patients with ER-positive and node-positive early breast cancer.

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Efficacy and safety of leuprorelin acetate 6-month depot, TAP-144-SR (6M), in combination with tamoxifen in postoperative, premenopausal patients with hormone receptor-positive breast cancer: a phase III, randomized, open-label, parallel-group comparative study

Breast Cancer ◽

10.1007/s12282-016-0691-6 ◽

2016 ◽

Vol 24 (1) ◽

pp. 161-170 ◽

Cited By ~ 5

Author(s):

Junichi Kurebayashi ◽

Tatsuya Toyama ◽

Shuuji Sumino ◽

Eri Miyajima ◽

Tsukasa Fujimoto

Keyword(s):

Breast Cancer ◽

Hormone Receptor ◽

Phase Iii ◽

Efficacy And Safety ◽

Open Label ◽

Leuprorelin Acetate ◽

Hormone Receptor Positive ◽

Parallel Group ◽

Premenopausal Patients ◽

Positive Breast Cancer

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HER-2/neu and p53 Expression Versus Tamoxifen Resistance in Estrogen Receptor–Positive, Node-Positive Breast Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2000.18.20.3471 ◽

2000 ◽

Vol 18 (20) ◽

pp. 3471-3479 ◽

Cited By ~ 114

Author(s):

Donald A. Berry ◽

Hyman B. Muss ◽

Ann D. Thor ◽

Lynn Dressler ◽

Edison T. Liu ◽

...

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Postmenopausal Women ◽

Positive Node ◽

P53 Expression ◽

Node Positive ◽

Er Positive ◽

Her 2 ◽

P53 Status ◽

Positive Breast Cancer

PURPOSE: An association between the overexpression of proto-oncogene HER-2/neu and resistance to tamoxifen in estrogen receptor (ER)–positive primary and metastatic breast cancer has been suggested. We examine a possible interaction between HER-2/neu or p53 expression and tamoxifen effectiveness in patients with ER-positive, node-positive disease treated with cyclophosphamide, doxorubicin, and fluorouracil in a large adjuvant chemotherapy trial (Cancer and Leukemia Group B [CALGB] 8541). Tamoxifen assignment was not randomized—physician discretion was used for premenopausal and postmenopausal women. Trial protocol then specified assignment to postmenopausal women with ER-positive tumors, although not all took tamoxifen. PATIENTS AND METHODS: CALGB 8541 assessed HER-2/neu expression in patients with ER-positive disease by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) and amplification by differential polymerase chain reaction (PCR). IHC assessed expression of p53. Univariate and multivariate proportional hazards models assessed tamoxifen–HER-2/neu status interactions and tamoxifen-p53 status interactions. RESULTS: HER-2/neu status was available for 651 patients with ER-positive disease; 650, 608, and 353 patients were assessed by IHC, PCR, and FISH, respectively. Approximately one half received tamoxifen. Reduction in risk of disease recurrence or death resulting from tamoxifen was approximately 37% (32% with overexpression and 39% with normal expression of HER-2/neu; n = 155 by IHC). The tamoxifen–HER-2/neu status interaction was not significant in multivariate analysis of all three HER-2/neu assessment methods. Tamoxifen-p53 interaction did not significantly predict outcome. CONCLUSION: Disease-free and overall survival benefit of tamoxifen in patients with ER-positive, node-positive breast cancer does not depend on HER-2/neu or p53 status. Our data suggest that neither HER-2/neu nor p53 expression should be used to determine assignment of tamoxifen.

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Adjuvant CMFVP versus adjuvant CMFVP plus ovariectomy for premenopausal, node-positive, and estrogen receptor-positive breast cancer patients: a Southwest Oncology Group study.

Journal of Clinical Oncology ◽

10.1200/jco.1996.14.1.46 ◽

1996 ◽

Vol 14 (1) ◽

pp. 46-51 ◽

Cited By ~ 21

Author(s):

S E Rivkin ◽

S Green ◽

J O'Sullivan ◽

A B Cruz ◽

M D Abeloff ◽

...

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Disease Free Survival ◽

Premenopausal Women ◽

Operable Breast Cancer ◽

Breast Cancer Patients ◽

Node Positive ◽

Er Positive ◽

Premenopausal Patients ◽

Positive Breast Cancer

PURPOSE To determine whether the addition of surgical ovariectomy to standard chemotherapy prolongs disease-free survival (DFS) and overall survival in premenopausal patients with estrogen receptor (ER)-positive operable breast cancer with positive axillary nodes. PATIENTS AND METHODS Three hundred fourteen premenopausal patients with ER-positive, node-positive breast cancer were enrolled between July 1979 and July 1989. Patients were stratified according to number of involved nodes and type of primary surgery and randomized to receive either of the following: (1) cyclophosphamide 60 mg/m2/d by mouth for 1 year, methotrexate 15 mg/m2 intravenously (i.v.) weekly for 1 year, fluorouracil (5-FU) 400 mg/m2 i.v. weekly for 1 year, vincristine .625 mg/m2 i.v. weekly for the first 10 weeks, and prednisone weeks 1 to 10 with doses decreasing from 30 mg/m2 to 2.5 mg/m2 (CMFVP); or (2) bilateral ovariectomy followed by CMFVP. RESULTS The median follow-up time is 7.7 years and the maximum 13.2 years. Treatment arms are not significantly different with respect to either survival or DFS (one-sided log-rank, P = .55 and .70, respectively). The 7-year survival rate is 71% on the CMFVP arm and 73% on CMFVP plus ovariectomy. No significant differences were observed in node or receptor level subsets. CONCLUSION We conclude that, in this study, the addition of ovariectomy did not improve results over chemotherapy alone in the treatment of premenopausal women with node-positive, ER-positive, operable breast cancer. Our sample size was too small to detect a small improvement. The death hazards ratio of CMFVP/CMFVP plus ovariectomy was 1.22 (95% confidence interval [CI], .79 to 1.89).

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